rs10520541

Positions:

• chr4-182759452-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080477.4(TENM3):​c.4892+4193C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,234 control chromosomes in the GnomAD database, including 1,970 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (1970 hom., cov: 33)
• Consequence: TENM3 NM_001080477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM3	NM_001080477.4	c.4892+4193C>G		intron_variant		ENST00000511685.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM3	ENST00000511685.6	c.4892+4193C>G		intron_variant		5	NM_001080477.4	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23694 AN: 152116 Hom.: 1970 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23710 AN: 152234 Hom.: 1970 Cov.: 33 AF XY: 0.156 AC XY: 11634 AN XY: 74422

Gnomad4 AFR AF: 0.0979

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.186

Alfa AF: 0.157 Hom.: 245

Bravo AF: 0.154

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.65
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10520541; hg19: chr4-183680605;